The presence of hypoxic cells in tumors is believed to be the limiting factor for complete control of tumors by radiotherapy. Fortunately, hypoxic cells undergo reoxygenation during the course of fractionated radiation. The vascular function in tumors may greatly influence the degree of reoxygenation of hypoxic cells and thus the curability of tumors by radiotherapy. We intend to measure various vascular parameters, i.e. vascular volume, vascular permeability, and blood flow rate in experimental animal tumors using the radioisotopic method during and after fractionated radiation. We will also evaluate the relationship between the vascular functions, hypoxic cell fraction, pH and pO2 in the tumors. We will also elucidate the vascular change caused by fractionated radiation in normal tissue (skin and muscle). This information is important in devising an effective radiation schedule to cause preferential damage in tumors with minimal normal tissue damage in the treatment of human cancer with radiotherapy. It has become increasingly evident that hyperthermia alone or in combination with radiotherapy or chemotherapy may be a potent modality in the treatment of malignat tumors. The blood flow rate plays the most important role in the preferential effect of hyperthermia on tumors, since the elevation of temperature in tumors and normal tissues by heat is closely related to heat dissipation by blood flow. Furthermore, the intratumor environment, i.e. pO2, pH and nutritional status, which is known to influence the thermosensitivity of cells, may be closely related to the vascular function in tumors. The effect of heat in a single and multiple doses on the vascular function in tumors and normal tissues will be studied. The relationship between the vascular function, intratumor environments, cell survival, and hypoxic cell fraction will then be investigated. We will also investigate the combined effect of radiation and hyperthermia on the vascular function in tumors and normal tissues and on the intratumor environment. This information is needed to devise an effective time dose schedule and sequence of radiotherapy and hyperthermia in the clinical application of these two modalities.